2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazoniol-5-yl]ethyl dihydrogen diphosphate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 Jan - 24 Jan 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Partition coefficient of the test item was calculated based on the ratio of its water solubility and its octanol solubility (based on OECD 105).

Qualifier:

equivalent or similar to guideline

Guideline:

other: Based on determination of ratio n-octanol solubility vs. aqueous solubility. Solubility determination accordingto OECD guideline 105, determination of octanol solubility based on principle of OECD guideline 105.

Qualifier:

according to guideline

Guideline:

other: EU method A.8.

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Storage conditions: ambient temperature (10 to 30 °C)

Analytical method:

high-performance liquid chromatography

Type:

log Pow

Partition coefficient:

-4.9

Temp.:

20 °C

Remarks on result:

other: pH not measured

 

Results
Table 1 – Preliminary visual estimation of n-octanol solubility

Amount of test item [mg]	Added volume of n-octanol [mL]	Total volume of n-octanol [mL]	Stirring time [h]	Appearance of mixture
22.5	2	2	0.5	Not dissolved
	8	10	0.5
	90	100	2	Very turbid

 

The solubility of the test item in n-octanol was: c_s^n-octanol< 225 mg/L.

Calculation of Partition Coefficient from Preliminary Test
The calculation was done with the result of the preliminary estimation of water solubility determined in the study report reference [4.8 -1], i.e. c_s^water= 77 g/L and the c_s^n-octanolvalue above.

It was calculated to be: log P_OW< -2.5

Using KOWWIN, the calculated value was -0.1.

Due to the calculations the partition coefficient was determined based on the ratio of the individual solubilities the test item in water and octanol. The individual octanol solubility was determined using the flask method. The shake flask method and HPLC method were not applicable due to the low log P_OW.

Determination of solubility in n-octanol – Flask Method
The n-octanol solubility was calculated from the measured and unrounded concentration values (not from the rounded values given in table 2).

Table 2 – n-octanol Solubility Experiments of the Test Item

Experiment	72 h experiment	96 h experiment	120 h experiment	Blank experiment (120 h)
Test item amount [mg]	67.9	67.9	76.0	--
Octanol amount [mL]	50
Stirring time at 30 °C [h]	72	96	120	120
Aliquot of the flasks [mL]	10
Volume of the aqueous phase used for the extraction [mL]	3
Dilution factor	0.4
Measured concentration [mg/L]	2.58 2.64	2.63 2.64	1.31 1.35	-- --
Mean concentration [mg/L]	2.61	2.63	1.33	--
n-octanol solubility [mg/L]	1.04	1.05	0.53	--

 

In a first test series with shorter stirring times, the results of the 3 experiments were in the same order of magnitude as in the reported second test series but they showed a larger variation. Thus the test series was repeated (see Table 2). It is  likely that the result of the 120 h stirring time experiment is an outlier. As a conservative approach, the highest n-octanol solubility was taken as a final result.

The n-octanol solubility of the test item at 20 °C was determined to be 1.1 mg/L.

Calculation of Partition Coefficient from Individual Solubilities
In the study report 20160198.05, the water solubility of the test item at 20 °C was c_s^water= 77 g/L. In this project, the n-octanol solubility of the test item at 20 °C was c_s^n-octanol= 1.1 mg/L. Thus, the partition coefficient was calculated to be:

log P_OW = -4.9

Description of key information

log P_OW = -4.9 at 20 °C (Calculation, EU Method A.8.)

Key value for chemical safety assessment

Log Kow (Log Pow):

-4.9

at the temperature of:

20 °C

Additional information

Partition coefficient was determined based on the ratio of the individual solubilities of the test item in water and octanol. The individual octanol solubility was determined using the flask method. The shake flask method and HPLC method were not applicable due to the low log P_OW.